The identification of new pharmacophores is of paramount biomedical importance and natural products have recently been regaining attention for this endeavor.1 This renaissance is closely tied to the successful exploitation of the marine environment which harbors unmatched biodiversity that is presumably concomitant with chemical diversity.2 In particular, marine cyanobacteria are prolific producers of bioactive secondary metabolites,3 many of which are modified peptides or peptide-polyketide hybrids with promising antitumor activities, such as dolastatin 10,4 curacin A,5 and apratoxin A.6 As a result of ongoing investigations to identify new drug leads from cyanobacteria, we report here the biological characterization of activity for class of a marine cyanobacterial metabolites and synthetic analogues with novel chemical scaffold and nanomolar antiproliferative activity. These findings provide new alternatives to address unmet needs in the treatment of proliferation diseases and disorders.
Modulation of cellular activity by apratoxins may be beneficial for cancer treatment and for immunosuppression, e.g., based on downregulation of receptors, inhibition of STAT3 activity and of T-cell activation. As such, other diseases that may be treated with apratoxin-based agents include other diseases where receptor downregulation may be beneficial, e.g., autoimmune diseases, some which may be associated with chemokine receptors (e.g., multiple sclerosis), or inflammation. These findings provide new alternatives to address unmet needs in the treatment of the aforementioned diseases, disorders, and symptoms thereof. Modulation of cellular activity by apratoxins may also be beneficial to disorders that are associated with enhanced secretory pathway activity.